Studies at our center have indicated that normal subjects receiving a high-salt diet had lower plasma concentrations of quinidine than when they were receiving a low-salt diet. The mechanism underlying this effect is unknown. Recent studies in other laboratories have suggested that salt loading may increase expression of cytochrome P450 involved in the renal metabolism of eicosanoids. However, no data are available on the effects of salt loading on hepatic P450-mediated drug metabolism. Our data with quinidine are consistent with the hypothesis that salt loading increases P450 activity, thereby accounting for decreased concentrations in salt-loaded subjects. This study is designed to elucidate the formal pharmacokinetics of quinidine with salt loading and salt restriction. These data will then allow further studies of underlying mechanism(s).